This invention relates to novel taste-masked pharmaceuticals and to taste-masked pharmaceuticals capable of being chewed without producing a bitter taste. In one embodiment of the invention a pharmaceutical composition comprised of a coated acetaminophen core that masks the bitter and unpleasant taste of acetaminophen is provided. A method of producing chewable tablets incorporating the coated acetaminophen is also described. The coating composition and the method of producing chewable tablets may be modified to provide taste-masking properties to a large number of unpleasant tasting drugs.
In a preferred embodiment of this invention, the formulation comprises a tablet which is further comprised of acetaminophen coated with a combination of polymers. In this embodiment, the acetaminophen chewable tablets do not exhibit the bitter and unpleasant taste normally associated with acetaminophen. In other embodiments, taste-masked dosage forms comprised of a number of antibiotics, and other pharmaceutical agents are provided. In each of these embodiments, excipients and other additives may be added to aid solubility and/or compressibility.
An oral dosage form is the preferred route of administration of acetaminophen and other pharmaceutical compounds because it provides easy, low cost administration. However, patient compliance becomes an important factor, especially when administering pharmaceuticals to children. Children generally show poor compliance with non-chewable tablets. Traditional non-chewable tablets generally show poor compliance in children, because they have trouble swallowing whole tablets. Part of the solution to this compliance problem is the use of chewable tablets as the administration vehicle. Chewable tablets are quite common and popular for solving the compliance problem, but when bitter or unpleasant tasting active agents, such as acetaminophen, are to be incorporated into chewable tablets, there is a need to mask the taste of the drugs. Otherwise, whatever increased compliance is obtained by using a chewable tablet will be lost to the unpleasant taste.
Conventional taste-masking techniques, for example, sweeteners and flavoring agents, may often be used. However, when a particularly unpleasant tasting active agent is to be administered, such as acetaminophen, these traditional sweeteners or flavoring agents are not as effective as certain embodiments of the invention described herein.
Alternative approaches of the prior art include microencapsulating unpleasant tasting active agent in a coating of ethyl cellulose or a mixture of ethyl cellulose and hydroxypropyl cellulose or other cellulose derivatives to provide chewable taste-masked products. These prior art products, however, suffer from the disadvantage that the polymer coating releases the active agent in an inconsistent fashion and may not provide immediate release. This may be due to a lack of an adequate amount of plasticizer in prior art chewable capsules to provide the necessary integrity for consistent release.
To provide chewable, taste-masked capsules with consistent release qualities microencapsulation with cellulose derivatives requires a plasticizer, for example, polyethylene glycol, among others, an adequate amounts to soften the coating and provide elasticity, or chewability. Elastic qualities are highly desirable in taste-masked microcapsules, because these qualities aid the capsule to resist fracture or rupture during chewing.
In one aspect of this invention, adequate supplies of plasticizer are incorporated into the polymeric cellulose coating to provide chewable capsules of greater integrity, i.e., the ability to avoid rupture or fracture during chewing than prior art chewable cellulose coated capsules.
In a second aspect of this invention, it has surprisingly been found that the incorporation of adequate amounts of a low temperature film forming polymer with cellulose polymers or other high temperature film forming polymers into the polymeric coating of a microcapsule will provide superior elastic (chewable) and taste-masked characteristics without causing delay of drug release when combined in accordance with this invention.
From a manufacturing cost standpoint, it is desirable to have chewable, taste-masked microcapsules that are large (0.25-1 mm in diameter), because larger microcapsules are easier to manufacture and package, and are less expensive to produce than are smaller microcapsules. However, an increase in size makes fracture during chewing and the release of drug from the microcapsule more likely to occur especially when there is an inadequate amount of plasticizer or other component included to provide elasticity. A larger sized microcapsule requires greater elasticity to minimize the likelihood that a fracture will occur and active agent will be released. There is therefore a need in the art of pharmaceutical formulation to provide encapsulating coatings capable of being formulated into chewable microcapsules as large as about 1.5 mm., that will not release drugs during chewing.
Prior art chewable microcapsules also suffer from the disadvantage that they are formulated using a technique known as coacervation (phase separation). The coacervation technique itself suffers from certain disadvantages. First, the technique requires the use of hydrocarbon and other flammable organic solvents, for example, cyclohexane, which are explosive and present problems in large scale manufacturing. Second, the technique is expensive, because of the additional costs associated with the regulatory compliance (EPA) relative to the method aspect of the invention described herein. Third, the process is very sensitive, and sometimes leads to reproducibility problems.
It is therefore an object of this invention to provide an improved orally active pharmaceutical composition that serves to taste-mask active agents. It is a further object of this invention to provide a chewable tablet or capsule that taste masks pharmaceutically active agents that are unpleasant in taste to increase patient compliance, especially in children.
It is an additional object of this invention to provide a chewable taste-masked formulation that can provide immediate release of an active compound as soon as it reaches the stomach. It is an additional object of this invention to provide a taste-masked formulation in "sprinkle" form that can provide immediate release of active agent in the stomach, delayed release of the active agent in the upper intestinal tract (duodenum, jejunum, or ileum) or sustained release of the active agent.
It is an additional object of this invention to provide chewable tablets of acetaminophen which do not exhibit the bitter, unpleasant taste characteristic of acetaminophen.
It is a further object of this invention to provide a method of producing taste-masked chewable pharmaceutical formulations utilizing an aqueous based formulation and an efficient process relative to the prior art methods such as coacervation or conventional coating techniques.